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Concurrent chemoradiation therapy is the standard of care for patients with inoperable non-small cell lung cancer, but starting the dual treatments more than three days apart from each other can result in poorer overall survival and an 8 percent increased risk of death, according to research published in Clinical Lung Cancer this summer.

A good fraction of non-small cell lung cancer cases present as stage III, locally advanced, unresectable cancers, corresponding author Salma K. Jabbour, MD, and colleagues wrote—up to 35 percent. Clinicians have found concurrent chemo and radiotherapy are the best shot at prolonging survival for those patients, but, despite National Comprehensive Cancer Network guidelines mandating both therapies start on the same day, that’s not always the case.

“Although it might be intuitive chemotherapy and radiotherapy start on the same day with concurrent treatment, no studies are available to support this practice nor have any examined the possible effect of minor delays on patient outcomes,” Jabbour, a radiation oncologist at the Rutgers Cancer Institute of New Jersey, and co-authors said.

They said in some instances it actually makes sense to start chemo earlier than radiation therapy, like in the case of a patient with large-volume lung cancer or bulky lymph nodes. Sometimes physicians are unable to coordinate their schedules, or patients have to drive grueling distances to medical facilities.

“Ideally, we strive to begin dual modality therapy as simultaneously as possible; however, in practical terms, patients might not start both chemotherapy and radiotherapy on the same day,” Jabbour et al. wrote. “Therefore, we evaluated, on a national level, trends in the administration of concurrent chemoradiation therapy, factors associated with nonsynchronous delivery of dual therapy and how variations in start dates of chemotherapy and RT affected overall survival in non-small cell lung cancer patients.”

In a cohort of 11,119 patients in the National Cancer Database undergoing chemoradiation therapy, the researchers said less than half—48.6 percent—of individuals began concurrent therapy on the same day, as per national guidelines. Starting both therapies within six days of each other was associated with improved survival and a 7 percent reduced risk of death, while starting dual treatment within three days was linked to even longer survival.

In keeping with their initial hypothesis, the authors did find that starting concurrent chemoradiation therapy four to six days apart was associated with an 8 percent increased risk of death and poorer survival rates.

“A significant proportion of patients, nearly 50 percent, do not start RT and chemotherapy on the same day, which was historically dictated in many trials the standard of care for which unresectable non-small cell lung cancer is based on,” the authors wrote. “The results of our analysis suggest that these relatively minor variations in starting chemotherapy and RT as part of concurrent chemoradiation therapy could be detrimental to patient outcomes.”

The authors said their study prompts further research into the subject.

“In this population, nonsimultaneous initiation of chemoradiation therapy was associated with differences in overall survival,” Jabbour and colleagues said. “Further efforts to understand the mitigating factors and barriers that interfere with timely delivery of concurrent chemoradiation therapy are needed.”